LOCALIZATION OF Β-AMYLOID PLAQUES IN THE BRAINS OF WAR VETERANS, PARTICIPANTS OF THE DOD-ADNI STUDY

Abstract We examined the allocation of β-amyloid (Aβ) plaques in the brains of Veterans, long-time survivors of traumatic brain injury (TBI), and those, who did not report brain trauma, and compared it with a spatial distribution of Aβ plaques in the brains of participants of the ADNI program as well as with the pattern of the spatial distribution of Aβ in the brains of participants of ADNI with Alzheimer’s disease. This study included 675 community-dwelling male participants from the ADNI and DoD-ADNI databases (137 veterans, 131 cases of TBI, and 123 AD cases) 62 years old or older. We performed regression analysis, using a pseudo-randomization algorithm, and propensity-score inverse-probability weighting to equalize the subsamples for fourteen outcomes, 12 standardized uptake value ratio variables, and 0.79 and 1.11 cutoffs. Race, educational level, geriatric depression score, age when florbetapir-18 (18F) PET scans were performed, APOE genotype, and Modified Hachinski Ischemic Score were used as predictors. The pattern common for AD showed the highest levels of β-amyloid in the cingulate cortex as well as in the frontal, parietal, and temporal lobes. Veterans have shown a statistically significant increase of 18F concentration in the cerebellum gray matter along with a lower concentration of it in the whole cerebrum as well as in neocortical regions than patients, who did not participate in combats. The continuous exposition to micro-TBI events, which does not necessarily suppose the loss of consciousness or severe contusion likely can explain the high concentration of 18F in cerebellum gray matter in ex-combatants.

EPHB1 previously associated with Parkinson's disease (PD) (p=8.4e-6), and a locus containing two independent intron 1 variants on CSMD1, a known risk factor for autosomal dominant PD (p=1.5e-6).Complement inhibitor protein CSMD1 is a type 1 transmembrane cell adhesion molecule implicated in axonal guidance and the development, maintenance, and pruning of synapses in the adult brain.Intermediate hits include genes encoding cell adhesion molecules and a second complement inhibitor implicated in the regulation of synapses (TRAPPC9).This converging evidence points to cell adhesion proteins and complement mediated synaptic regulation in the etiology of Lewy body lesions.
Abstract citation ID: igad104.2235Cognitive disorders, particularly dementia, are a major cause of disability in the elderly population.Gait disturbances, decreased grip strength and memory complaints are early signs of dementia that can occur well before the disease manifests.To better understand the close interactions between the physical and cognitive domains, the concept of Motoric Cognitive Risk Syndrome (MCRS) has been proposed.We had 25 older adults (10 cognitively unimpaired and 15 with MCRS) generate multiple force pulses at 15% of their maximum voluntary contraction with a fixed duration of 2 seconds for each pulse in which participants must rely on visual spatial abilities to gauge the amount force required in real-time to reach the criterion target.We also assessed neurofilament light chain levels also a blood-based marker of neuronal loss.Our results indicate the MCRS group demonstrated blood oxygenation level dependent (BOLD) hyperactivity in visual cortical/hippocampal regions, parahippocampal regions, and dorsolateral prefrontal cortex.The MCRS group also demonstrated BOLD hypoactivity in primarily involved with movement, such as cerebellar lobules, supplementary motor areas, middle frontal gyrus, and prefrontal cortex areas.beuseful in tracking disease progression.We also found a significant strong positive correlation (0.83) between serum NFL levels and Right BOLD coefficients only for the CI group.This finding suggests that these motor task fMRI measures may be specific in tracking neurodegeneration in MCRS group.Overall, the current preliminary findings provide novel insights into the neurobiological mechanisms underlying early changes in Alzheimer's disease and related dementias.

IDENTIFYING MARKERS OF NEURODEGENERATION FOR MOTORIC COGNITIVE RISK SYNDROME
We examined the allocation of β-amyloid (Aβ) plaques in the brains of Veterans, long-time survivors of traumatic brain injury (TBI), and those, who did not report brain trauma, and compared it with a spatial distribution of Aβ plaques in the brains of participants of the ADNI program as well as with the pattern of the spatial distribution of Aβ in the brains of participants of ADNI with Alzheimer's disease.This study included 675 community-dwelling male participants from the ADNI and DoD-ADNI databases (137 veterans, 131 cases of TBI, and 123 AD cases) 62 years old or older.We performed regression analysis, using a pseudo-randomization algorithm, and propensity-score inverse-probability weighting to equalize the subsamples for fourteen outcomes, 12 standardized uptake value ratio variables, and 0.79 and 1.11 cutoffs.Race, educational level, geriatric depression score, age when florbetapir-18 (18F) PET scans were performed, APOE genotype, and Modified Hachinski Ischemic Score were used as predictors.The pattern common for AD showed the highest levels of β-amyloid in the cingulate cortex as well as in the frontal, parietal, and temporal lobes.Veterans have shown a statistically significant increase of 18F concentration in the cerebellum gray matter along with a lower concentration of it in the whole cerebrum as well as in neocortical regions than patients, who did not participate in combats.The continuous exposition to micro-TBI events, which does not necessarily suppose the loss of consciousness or severe contusion likely can explain the high concentration of 18F in cerebellum gray matter in ex-combatants.Objectives: To examine whether plasma biomarkers brainderived neurotrophic factor (BDNF), irisin, clusterin and BDNF/irisin ratio (BIR) could differentiate people with mild cognitive impairment (MCI) from cognitively normal (CN) individuals, and to explore their relations with cognitive performance.Methods: We included 124 participants with MCI and 126 CN participants from a community-based aged and cognitive health cohort.Plasma BDNF, irisin and clusterin were measured, and BIR was calculated.Global cognition was evaluated with Montreal Cognitive Assessment.T-tests, logistic regressions, and linear regressions were used to explore the relations between plasma biomarkers and cognitive function.Results: The plasma levels of irisin, but not BDNF, was significantly different between MCI and CN groups.Higher irisin concentration was associated with increased probability for MCI (OR: 1.06, p = 0.004) after adjusting for covariates.By contrast, BDNF, but not irisin, was linearly correlated with cognitive performance (β = 0.14, p = 0.033).BIR values were positively correlated with cognitive performance (β= 0.14, p = 0.036), and significant differences on BIR values existed between MCI and CN groups.The MCI risk decreased by 53% (OR=0.47,p = 0.043) with each unit increase in BIR values after adjusting for covariates.Plasma BDNF and irisin concentrations increased with aging, whereas BIR values remained stable across the ages.
No significant results of clusterin were observed in the above analyses.Conclusion: Plasma BIR is a potentially reliable indicator which not only reflects the odds of the presence of MCI but also directly associates with cognitive performance in the aged population.

RACE DIFFERENCES IN THE RELATIONSHIP BETWEEN HIGH AND VARIABLE BLOOD PRESSURE AND DOMAIN-SPECIFIC COGNITIVE CHANGE
Michael Oliver 1 , Cassandra Morrison 2 , and Sondos El-Hulu 1 , 1. Belmont University, Nashville, Tennessee, United States,2. Montreal Neurological Institute,McGill University,Montréal,Quebec,Canada Elevated blood pressure (BP), or hypertension, is a risk factor for several health conditions including Alzheimer's disease.High BP in early-and mid-life is associated with cognitive decline, whereas research is mixed regarding BP and cognition in late-life.Moreover, hypertension disproportionately affects minority populations.Consequently, the effects of hypertension on cognition may differ by race.The present study investigates the relationship between BP and cognition.4419 older adults (Black, n=1189; White, n= 3230), with 32116 follow-ups for a maximum of 10-years were included from the Rush Alzheimer's Disease Center.Results reveal individuals with high BP exhibit significantly greater declines in global cognition compared to normal BP, regardless of race.When stratifying high BP by race, Blacks exhibit greater declines in working memory and perceptual speed, whereas Whites exhibit greater declines in episodic memory, semantic memory, and visuospatial ability compared to normal BP.Blacks with high BP exhibit greater decline in perceptual speed compared to variable BP, whereas no cognitive domain was worse in Whites with high BP compared to variable.When stratifying variable BP by race, Blacks exhibited greater decline in working memory compared to normal BP.Alternatively, Whites exhibited greater decline in episodic memory, semantic memory, working memory, and global cognition compared to normal and high BP counterparts.Our findings reveal racial differences in the relationship between BP and cognitive decline.Specifically, Blacks and Whites with high and variable BP experience cognitive decline in different cognitive domains, which may give insight into differences in disease trajectory and cognitive outcomes.
Abstract citation ID: igad104.2239Marrium Mansoor, and Benjamin Katz, Virginia Tech, Blacksburg, Virginia, United States Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by executive function (EF) deficits that may impact academic performance, workplace achievement, and other outcomes throughout adulthood.Although 6.76% of adults worldwide may be affected by ADHD, the interplay of early life factors and genetic risk is still not fully understood, especially in the context of cognitive function in later life.While literature suggests that early life experiences may moderate the links between genetic risk for ADHD and later life

THE EFFECT OF EARLY SCHOOLING EXPERIENCES AND ADHD POLYGENIC RISK ON COGNITIVE PERFORMANCE IN LATE LIFE
Edward Ofori 1 , Madeline Hooten 2 , Marcus Ortega 2 , Jordan Barajas 2 , and Dara James 3 , 1. Arizona State University, Tempe, Arizona, United States, 2. Arizona State University, Phoenix, Arizona, United States, 3. University of South Alabama, Mobile, Alabama, United States